Drawing on the broad scientific expertise of faculty at Washington University in St. Louis and collaborators and consultants from other institutions, we propose to build on existing transdisciplinary approaches and create a center to address mechanisms of obesity and cancer, from cell to society. We include projects that move beyond traditional risk factor-cancer associations to look at multilevel and multigenerational associations as well as the interaction of traditional cancer risk behaviors. We leverage the unique opportunity Missouri provides to study human populations given its diversity across race/ethnicity and socioeconomic status. We will delineate mechanisms by which preconception diet, nutrition & built environment polices impact inactivity and physical activity and energy balance to influence body weight and carcinogenesis across the life course. Specifically we aim to: 1. Investigate in a mouse model the effect of maternal high fat diet and changes in metabolic bioenergetics on prostate gland development and susceptibility to prostate cancer in male mouse offspring; 2. Study the role of physical activity and obesity in post-prostatectomy urinary and sexual function; 3. Develop models of obesity across the life course and generations incorporating biologic, clinical and social determinants of risk and mortality, which can be applied to different cancer outcomes, using non-Hodgkin Lymphoma as the initial platform; 4. Study policies relating to nutrition and built environment that impact energy balance and obesity; 5. Train postdoctoral fellows in a transdisciplinary environment to pursue careers in energetics and cancer and expose scholars from across our university to transdisciplinary work in obesity and cancer; 6. Foster scientific synergy via smaller-scale innovative transdisciplinary research that builds on the Center's theme and resources; and 7. Maximize efficiency and productivity of TREC-related studies and cores by building an outstanding transdisciplinary center supported by outstanding administrative, budgetary, and technology resources. To address these aims, we propose four research projects and five cores that form a cohesive, transdisciplinary center focused on research, training/career development, and dissemination.